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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis E virus is responsible for both sporadic and epidemic hepatitis in developing countries. The nonenveloped virus is 27-34 nm in diameter and has been shown to contain a single-strand, positive-sense, polyadenylylated RNA genome of approximately 7.5 kilobases. The nucleotide sequence of the Burma strain of hepatitis E virus has been reported and three open reading frames (ORFs) have been identified. The deduced amino acid sequence from each of these ORFs was used to synthesize overlapping peptides (decamers overlapping at every fourth amino acid) on a solid phase. These peptides were then tested in an ELISA with pooled acute-phase sera from known cases of enterically transmitted non-A, non-B hepatitis collected in the Sudan. Linear B-cell epitopes were identified in all three ORFs. Epitopes were identified throughout the polyprotein encoded by ORF1, but they appeared to be particularly concentrated in the region of the RNA-dependent RNA polymerase. Distinct epitopes were identified in the presumed structural protein encoded by ORF2, and one epitope was identified close to the carboxyl terminus of the protein encoded by ORF3. These data precisely pinpoint linear B-cell epitopes recognized by antibodies from patients with acute hepatitis E and identify an antibody response directed against the RNA-dependent RNA polymerase.
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PMID:Human linear B-cell epitopes encoded by the hepatitis E virus include determinants in the RNA-dependent RNA polymerase. 137 90

Hepatitis E virus (HEV) is the major causative agent of hepatitis E or what was formerly known as enterically transmitted non-A, non-B hepatitis. The disease has a worldwide distribution but occurs principally in developing countries in any of three forms: large epidemics, smaller outbreaks, or sporadic infections. Genetic variation of different HEV strains was previously noted and it will be important to determine the extent to which this variation may pose problems in the diagnosis and treatment of HEV infection. To analyze differences at the genetic level between HEV(Mexico; M) and the previously characterized HEV(Burma; B) and HEV(Pakistan; P) isolates, overlapping cDNAs were cloned from samples obtained from an infected human and an experimentally inoculated cynomolgus macaque. These cDNA clones, representing the nearly complete (7185-bp) genome of HEV(M), confirmed an expression strategy for the virus that involves the use of 3 forward open reading frames (ORFs). The HEV(M) strain has an overall 76 and 77% nucleic acid identity with the HEV(B) strain and HEV(P) strain, respectively; however, the degree of sequence variation was not uniform throughout the viral genome. A hypervariable region was identified in ORF1 that exhibited a 58 and 54% nucleic acid sequence and 13% amino acid similarity with the Burma strain and the Pakistan strain, respectively. A large number of the nucleotide differences occurred at the third codon position, with the deduced amino acid sequences similarity of 83, 93, and 87% between HEV(M) and HEV(B) isolates in ORF1, ORF2, and ORF3, respectively, and with 84, 93, and 87% amino acid identities between HEV(M) and HEV(P) isolates in ORF1, ORF2, and ORF3, respectively. The nucleotide sequences derived from the highly conserved regions of HEV genome will be useful in developing polymerase chain reaction-based tests to confirm the viral infection. Knowledge of the extent of the sequence variation encountered with HEV will not only aid in the future development of diagnostic and vaccine reagents but also further our understanding of how HEV strain variation might impact the pathological outcome of infection.
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PMID:Molecular cloning and sequencing of the Mexico isolate of hepatitis E virus (HEV). 144 13

Enterically transmitted non-A, non-B hepatitis virus (HEV), the causative agent for sporadic and large epidemic outbreaks in developing countries, contains a positive-sense single-stranded RNA genome. The genome of the virus encodes three open reading frames (ORF1, ORF2, and ORF3). The gene segment corresponding to the small open reading frame (ORF3), overlapping between ORF1 and ORF2, was synthesized by reverse transcription-polymerase chain reaction (RT-PCR) from a number of previously identified HEV-positive clinical specimens. A DNA fragment of 166 bp was consistently obtained from all the clinical specimens. This small fragment was cloned, sequenced, and found to contain an open reading frame encoding only 41 amino acid residues. Comparison of our results with that of geographically related Burma HEV suggests a major inframe deletion of 246 bp in the ORF3 of Indian strain. The protein encoded by ORF3 does not appear to be useful for early serodiagnosis as a synthetic peptide deduced from the truncated ORF3 failed to show any demonstrable immunoreactivity against HEV-infected acute phase sera in an enzyme-linked immunosorbent assay.
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PMID:Indian hepatitis E virus shows a major deletion in the small open reading frame. 153 53

The etiologic agent responsible for epidemics of enterically-transmitted non-A, non-B hepatitis has been molecularly characterized as the hepatitis E virus (HEV). The cloning of a portion of the Burma strain of HEV (HEV(B); 'Old World' strain) has been described together with the isolation of a contiguous overlapping set of cDNA clones representing the entire viral genome. Our studies have led to a model for the genomic organization of this positive strand, polyadenylated, RNA virus. Molecular clones encompassing the entire genome were also isolated from a cDNA library made from the Mexico strain of HEV (HEV(M); 'New World' strain). The translated nucleotide sequence of the Mexico isolate confirmed the genomic organization as first interpreted for HEV(B). This refers to the utilization of at least three different discontinuous open reading frames for protein expression and their apparent organization into 5' nonstructural and 3' structural gene regions. The comparison of the two strains identified a localized area of divergent nucleic and amino acid sequence that was previously reported in the region encoding the nonstructural gene(s) (ORF1). The HEV expression strategy involves at least two subgenomic poly-A transcripts that are co-terminal with the 3' end of the virus. Cross-reactive (type-common) epitopes are shared between the two divergent strains. It will be important to determine in future studies if any correlation exist between the viral pathobiology in animals or humans and the primary sequence of the virus.
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PMID:Hepatitis E virus. Comparison of 'New and Old World' isolates. 182 10

Hepatitis E virus (HEV) is a polyadenylated, positive-stranded RNA virus which is a major cause of enterically transmitted non-A, non-B hepatitis in many developing countries. The viral genome contains three different open reading frames (ORFs): ORF1, which is believed to encode nonstructural proteins, and ORF2 and ORF3, which are believed to encode structural proteins. The full-length putative structural proteins encoded by ORF2 and ORF3 of HEV have been cloned and expressed in recombinant vaccinia virus. Proteins encoded by ORF2 and ORF3 when expressed in vaccinia virus are recognized by pooled sera obtained from individuals with acute hepatitis E. Vaccinia-expressed viral gene products of HEV will have utility in characterizing the cell-mediated immune response to HEV.
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PMID:Expression of hepatitis E virus putative structural proteins in recombinant vaccinia viruses. 749 58

The recently characterized fecal-orally transmitted agent of hepatitis E (formerly known as enterically transmitted non-A, non-B hepatitis) has been determined to be a new type of positive strand RNA virus. The complete sequencing of four different geographic isolates of the hepatitis E virus (HEV) has confirmed a similar genetic organization not previously recognized in nonenveloped positive strand RNA viruses. The approximately 7.5 kb RNA genome (including polyA tail) has nonstructural genes located at the 5' end and structural genes at the 3' end. Expression of these viral genes occurs in at least 3 different forward open reading frames. The largest open reading frame begins 27 nucleotides (nt) downstream of the apparent noncoding 5' end and extends 5,079 nt. Multiple nonstructural gene motifs/domains have been recognized in this 5' ORF1 including a methyltransferase, a papain-like protease, a helicase and the RNA-dependent, RNA polymerase. The second major ORF2 begins 37nt downstream of ORF1 and extends 1980 nt before terminating 65 nt upstream of the polyadenylation site. A third ORF of only 369 nt was identified by immunoscreening experiments as encoding an immunogenic epitope of the virus. Expression of the downstream ORF2 may occur through internal subgenomic RNA initiation at a sequence element found to have homology to internal RNA initiation sequences in Sindbis virus. This element in the HEV genome maps near the apparent 5' end of one of two identified subgenomic messages. The genomic organization and expression of HEV will be discussed and a hypothesis presented regarding the viral replication strategy.
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PMID:Molecular organization and replication of hepatitis E virus (HEV). 821 99

A variant of hepatitis E virus (HEV), designated HEV US-1, was identified in a hepatitis patient in the United States (US); the patient had no history of travel to areas where HEV is endemic. Nucleotide sequences were obtained from the 5' end of open reading frame (ORF) 1 (1418 nt), the 3' end of ORF1 (1359 nt), the entire ORF2 and ORF3 regions, and the 3'-untranslated region (2127 nt). The HEV US-1 strain is significantly divergent from other human HEV isolates with nucleotide identities ranging from 76.8 to 77.5%. Phylogenetic analyses indicate that HEV US-1 and a recently discovered HEV variant from swine may represent separate isolates of a new strain of HEV, significantly divergent from the Mexican and Burmese strains. Synthetic peptides derived from the carboxyl amino acids of ORF2 and ORF3 were shown to be useful for detecting exposure to HEV. In addition, IgM class antibodies directed against HEV US-1 synthetic peptides were detected in the US patient infected with HEV US-1, but were absent using synthetic peptides from the Burmese or Mexican strains of HEV. A preferential reactivity to HEV US-1 specific peptides has lead to the identification of a second isolate of this virus also from a patient with acute hepatitis from the US. The discovery of these HEV variants may be important in understanding the worldwide distribution of HEV infection.
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PMID:The sequence and phylogenetic analysis of a novel hepatitis E virus isolated from a patient with acute hepatitis reported in the United States. 951 22

Recent studies have reported and provided nucleotide sequence data from divergent isolates of hepatitis E virus (HEV), including isolates from North America and Africa. Sera were investigated from 29 Chinese patients with a diagnosis of acute hepatitis and who were negative for hepatitis viruses A-E by serology (HEV was excluded by testing for IgG antibody only). To determine whether some patients were infected with HEV but had yet to seroconvert to antibody positivity, RT-PCR was carried out with primers designed within conserved sequences of the HEV open reading frame (ORF) 1 and ORF2 regions. Fifteen patients were found to harbour sequences related to HEV. Analysis of the HEV products revealed that nucleotide sequences from nine of the sera closely matched Burmese-like HEV sequences (more than 92% nucleotide identity across ORF1 and 88% in ORF2). The remaining six HEV isolates were similar to each other but divergent from all other known HEV sequences (74 to 83% nucleotide identity in ORF1 or ORF2). Phylogenetic analysis suggests that the six divergent isolates represent a fourth genotype of HEV, distinct from the previously described Burmese, Mexican and United States variants (genotypes 1, 2 and 3). This novel variant, referred to here as the Chinese genotype (genotype 4), may be responsible for a significant proportion of cases of acute hepatitis in China, as seen by the fact that 40% of the HEV-infected patients in this study were genotype 4 positive.
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PMID:A divergent genotype of hepatitis E virus in Chinese patients with acute hepatitis. 993 99

A novel single-stranded DNA virus, TT virus(TTV), has been reported recently. We detected TTV viral sequences by polymerase chain reaction using primers derived from nucleotide sequences of ORF1 and the 5' noncoding region of ORF2. Using primers of the 5' noncoding region, TTV DNA was detected in 21 of 25(84%) healthy individuals, suggesting that most TTV strains detected by these primers are almost harmless. In contrast, using primers of ORF1, which detect genotype 1a TTV that was reported to be a causative agent of posttransfusion hepatitis, TTV DNA was detected in only 3 of 25 healthy subjects and 3 of 27 acute and 9 of 72(12%) chronic non-A to G hepatitis patients. Whether these TTV strains actually cause hepatitis remains to be determined.
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PMID:[Detection of TT virus DNA in patients with non-A to G liver diseases]. 1039 Sep 86

Hepatitis E virus (HEV) is an important cause of epidemic and sporadic acute viral hepatitis in many developing countries, including India. We evaluated the genetic variability within two regions (a 476-nt long ORF1 segment and a 304-nt long ORF2 segment) from specimens collected during three outbreaks in the cities of Karnal (1987), Yamunanagar (1989), and Meerut (1996), India, and from one patient, residing in Lucknow, India, who had a case of sporadic hepatitis (1996). Within an outbreak, sequences in the ORF1 and ORF2 regions were 99.3-100.0% identical. However, when strains were compared between outbreaks, identity in the ORF1 and ORF2 region was 97.1-99.2 and 96.4-100.0%, respectively. A comparison of these sequences to previously published Indian ORF1 and ORF2 sequences revealed even lower similarities, 95.2-98.5 and 95.1-98.7%, respectively. One patient in the Meerut outbreak had genomic sequences that differed substantially from the other patients affected during this outbreak and probably reflected a sporadic infection. The sporadic hepatitis E strain from Lucknow clustered with a previously described HEV strain from a patient with fulminant hepatic failure (FHF). Our data suggest that the ORF1 and ORF2 segments can be used to study the molecular epidemiology of HEV infection and indicate that much remains to be determined about the genetic variability of Indian HEV strains.
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PMID:Genetic variability of hepatitis E virus within and between three epidemics in India. 1085 64


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